Recommendations for Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer ASCO Clinical Practice Gui

2. Introduction ASCO convened an expert panel to develop guideline recommendations for the use of anticoagulation in the prevention and treatment of venous thromboembolism (VTE) in patients with cancer.

3. Guideline Methodology: Systematic Review A comprehensive systematic review of the medical literature available through December 2006 on anticoagulation and the prevention of VTE in patients with cancer was conducted. Medline EMBASE CancerLit Cochrane Database of Abstracts of Reviews of Effects (DARE) National Guidelines Clearing House

4. Guideline Methodology (cont’d): Panel Members

5. Guideline Methodology (cont’d): Panel Members

6. Background Venous Thromboembolism (VTE) A leading cause of morbidity and mortality in patients with cancer Affects 4-20% of patients with cancer Appears to be increasing Burden Mortality Morbidity Other health outcomes Use of health care resources

7. Background Major Risk Factors Age Primary site of cancer (gastrointestinal, brain, lung, gynecologic, pancreatic, gastrointestinal, ovarian, renal, bladder, hematologic) History of VTE Hospitalization Major surgery Those receiving active therapy, including chemotherapy, antiangiogenic drugs, and hormonal therapy Metastatic disease Red cell growth factors Challenges and Opportunities Primary prophylaxis can reduce DVT, PE, and fatal PE Prophylaxis under-utilized

8. Clinical Questions Should patients with cancer receive anticoagulation for VTE prophylaxis while hospitalized? Should ambulatory patients with cancer receive anticoagulation for VTE prophylaxis during systemic chemotherapy? Should patients with cancer undergoing surgery receive perioperative VTE prophylaxis? What is the best method for treatment of patients with cancer with established VTE to prevent recurrence? Should patients with cancer receive anticoagulants in the absence of established VTE to improve survival?

9. 2007 Recommendations for Venous Thromboembolism Prophylaxis in Patients with Cancer Hospitalized patients with cancer should be considered candidates for VTE prophylaxis in the absence of bleeding or other contraindications to anticoagulation.

10. 2007 Recommendations for Venous Thromboembolism Prophylaxis in Patients with Cancer Ambulatory patients with cancer: Routine prophylaxis with an antithrombotic agent is not recommended. Patients receiving thalidomide or lenalidomide with chemotherapy or dexamethasone are at high risk for thrombosis and warrant prophylaxis. LMWH (low molecular weight heparin) or adjusted dose warfarin (INR~1.5) is recommended. This recommendation is based on extrapolation from studies of post-operative prophylaxis in orthopedic surgery and a trial of adjusted dose warfarin in patients with breast cancer. Randomized clinical trials evaluating antithrombotic agents in patients with multiple myeloma on thalidomide or lenalidomide are needed. Research is also urgently needed to identify better markers in ambulatory patients with cancer who are most likely to develop VTE.

11. 2007 Recommendations for Venous Thromboembolism Prophylaxis in Patients with Cancer, Continued Patients undergoing surgery: All patients undergoing major surgical intervention* for malignant disease should be considered for thromboprophylaxis. Eligible patients should receive pharmacological thromboprophylaxis with either low dose UFH (unfractionated heparin) or LMWH unless contraindicated because of a high risk for or active bleeding. Prophylaxis should be commenced preoperatively, or as early as possible in the postoperative period. *laparotomy, laparoscopy or thoracotomy lasting greater than 30 minutes

12. 2007 Recommendations for Venous Thromboembolism Prophylaxis in Patients with Cancer, Continued Patients undergoing surgery, continued: Mechanical methods may be added to pharmacological methods, but should not be used as monotherapy for VTE prevention unless pharmacological methods are contraindicated because of active bleeding. A combined regimen of pharmacologic and mechanical prophylaxis may improve efficacy in the patients at highest-risk. Prophylaxis should be continued for at least 7-10 days postoperatively and may be extended into the post discharge period for selected patients at high risk.** **residual malignant disease after operation, obesity, or previous history of VTE

13. 2007 Recommendations for Venous Thromboembolism Prophylaxis in Patients with Cancer, Continued Preventing recurrence in patients with cancer with established VTE LMWH is the preferred approach for the initial 5 to 10 days of anticoagulant treatment of the patient with cancer with established VTE. LMWH given for at least 6 months is also the preferred approach for long-term anticoagulant therapy. Vitamin K antagonists with a targeted INR of 2-3 are acceptable for long-term therapy when LMWH is not available. After 6 months, indefinite anticoagulant therapy should be considered for patients with active cancer. The insertion of a vena cava filter is only indicated for patients with contraindications to anticoagulant therapy and in those with recurrent VTE despite adequate long-term therapy with LMWH.

14. 2007 Recommendations for Venous Thromboembolism Prophylaxis in Patients with Cancer, Continued Preventing recurrence in patients with cancer with established VTE, continued In patients with central nervous system malignancies and in the elderly, anticoagulation is recommended for established VTE as described for other patients with cancer . Careful monitoring of anticoagulation is necessary to limit the risk of hemorrhagic complications. Anticoagulation should be avoided in the presence of active intracranial bleeding or preexisting bleeding diathesis such as thrombocytopenia (platelet count <50,000/mm3) or coagulopathy.

15. 2007 Recommendations for Venous Thromboembolism Prophylaxis in Patients with Cancer, Continued Improving survival in absence of established VTE Anticoagulants are not recommended to improve survival in patients with cancer without VTE. People with cancer should be encouraged to participate in clinical trials designed to evaluate anticoagulant therapy as an adjunct to standard anticancer therapies.

16. Recommended Dose: Venous Thromboembolism Prophylaxis/Treatment

17. Recommended Dose: Venous Thromboembolism Prophylaxis/Treatment

18. Relative contraindications for anticoagulation Active, uncontrollable bleeding Active cerebrovascular hemorrhage Dissecting or cerebral aneurysm Bacterial endocarditis Pericarditis, active peptic or other GI ulceration Severe, uncontrolled or malignant hypertension Severe head trauma Pregnancy (warfarin) Heparin-induced thrombocytopenia (heparin, LMWH) Epidural catheter placement

19. Types of Mechanical Methods Graduated compression stockings Intermittent pneumatic compression (IPC) Mechanical foot pumps

20. Special Considerations

21. Summary

22. Additional ASCO Resources This slide set and additional resources can be accessed at: http://www.asco.org/guidelines/vte Access the People Living With Cancer website for a Patient Guide and other patient-friendly information at http://www.cancer.net

23. ASCO Guidelines